A genetic variant of the sperm-specific SLO3 K+ channel has altered pH and Ca2+ sensitivities

To fertilize an oocyte, sperm must first undergo capacitation in which the sperm plasma membrane becomes hyperpolarized via activation of potassium (K(+)) channels and resultant K(+) efflux. Sperm-specific SLO3 K(+) channels are responsible for these membrane potential changes critical for fertilization in mouse sperm, and they are only sensitive to pH i However, in human sperm, the major K(+) conductance is both Ca(2+)- and pH i -sensitive. It has been debated whether Ca(2+)-sensitive SLO1 channels substitute for human SLO3 (hSLO3) in human sperm or whether human SLO3 channels have acquired Ca(2+) sensitivity. Here we show that hSLO3 is rapidly evolving and reveal a natural structural variant with enhanced apparent Ca(2+) and pH sensitivities. This variant allele (C382R) alters an amino acid side chain at a principal interface between the intramembrane-gated pore and the cytoplasmic gating ring of the channel. Because the gating ring contains sensors to intracellular factors such as pH and Ca(2+), the effectiveness of transduction between the gating ring and the pore domain appears to be enhanced. Our results suggest that sperm-specific genes can evolve rapidly and that natural genetic variation may have led to a SLO3 variant that differs from wild type in both pH and intracellular Ca(2+) sensitivities. Whether this physiological variation confers differences in fertility among males remains to be established.info:eu-repo/semantics/publishe

Conserved mechanism of bicarbonate-induced sensitization of CatSper channels in human and mouse sperm

To fertilize an egg, mammalian sperm must undergo capacitation in the female genital tract. A key contributor to capacitation is the calcium (C

Two-Stage Nonparametric Regression for Longitudinal Data

In the analysis of longitudinal data it is of main interest to investigate the existence of group and individual effects under correlated observations across time. In this paper, we develop a nonparametric two-step procedure that enables us to estimate group effects under a very general form of correlation across time. Moreover, we propose several methods to estimate the bandwidth and show their asymptotyc optimality. Since the asymptotic distribution is untractable, we develop a randomization test that is suitable for testing the group effects. Finally, we apply the estimation procedure, the bandwidth selection criteria and the randomization test to the data from the Iowa Cochlear Implant Project.This work was supported by Dirección General de Enseñanza Superior del Ministerio Español de Educación y Cultura and Universidad del País Vasco (UPV/EHU) under research grant PB95-0346

Nonparametric estimation of time varying parameters under shape restrictions

In this paper we propose a new method to estimate nonparametrically a time varying parameter model when some qualitative information from outside data (e.g. seasonality) is available. In this framework we make two main contributions. First, the resulting estimator is shown to belong to the class of generalized ridge estimators and under some conditions its rate of convergence is optimal within its smoothness class. Furthermore, if the outside data information is fullfilled by the underlying model, the estimator shows efficiency gains in small sample sizes. Second, for the implementation process, since the estimation procedure envolves the computation of the inverse of a high order matrix we provide an algorithm that avoids this computation and, also, a data-driven method is derived to select the control parameters. The practical performance of the method is demonstrated in a simulation study and in an application to the demand of soft drinks in Canada.nonparametric regression, Kernel estimators, time varying coefficients, bandwidth selection, estimation algorithm, seasonality

A comparative analysis of genetic diversity in Portuguese grape germplasm from ampelographic collections fit for quality wine production

Grapevine cultivars diversity is vast and full of synonyms and homonyms. Up to few decades ago characterization of grapevine was based on morphological characters. In the last decades, molecular markers were developed and have been used as tools to study genetic diversity in a range of different plant species. Fifty-six Portuguese accessions representative of ‘Vinhos Verdes’ and ‘Douro’ Controlled Designations of Origin (DOC) were analysed through DNA fingerprints generated by Random Amplified Polymorphic DNA (RAPD) and Inter Simple Sequence Repeat (ISSR). The study aimed to compare the effectiveness of RAPD and ISSR molecular techniques in the detection of synonyms, homonyms and misnames. RAPD and ISSR analysis enabled the detection of 36 different band patterns, reducing in about 36% the initial material. Several accessions grown under different names, between and within collections, were confirmed as the same genotype, namely Gouveio/Verdelho, Sousão Douro/Vinhão and Arinto Oeste/Pedernã. Similarly, some homonyms/misnames were also identified, namely within Azal Tinto and Rabigato accessions. RAPD and ISSR markers revealed to be adequate molecular techniques for grapevine varieties fingerprinting with advantages over other molecular procedures, contributing for a good management of grapevine collections

Estudo de sensibilidade das previsoes de superficie em Portugal pelo WRF face à variaçao das parametrizaçoes físicas

Ponencia presentada en: XXX Jornadas Científicas de la AME y el IX Encuentro Hispano Luso de Meteorología celebrado en Zaragoza, del 5 al 7 de mayo de 2008

SLO2.1/NALCN a sodium signaling complex that regulates uterine activity

Depolarization of the myometrial smooth muscle cell (MSMC) resting membrane potential is necessary for the uterus to transition from a quiescent state to a contractile state. The molecular mechanisms involved in this transition are not completely understood. Here, we report that a coupled system between the N